Amidoximo alkyl



United States Patent 3,118,904 N-(AMIDOXKMO ALKYL)-ENDO-PERHYDRO4,7-

METHANGISOINDOLES James W. Bolger, Canoga Park, Calif., assignor to Riker Laboratories, Inc, Northridge, Caiifi, a corporation of Delaware No Drawing. Filed July 27, 1962, Ser. No. 213,047 2 Claims. (Cl. 2-50319) This invention relates to compositions of matter classified in the art of chemistry as substituted isoindoles.

The invention sought to be patented resides in the concept of a chemical compound in which there is attached to the nitrogen atom, of an endo-perhydro-4,7- methanoisoindole nucleus an amidoximo lower alkyl substituent.

As used throughout the specification and in the claims the term lower alkyl and lower alkylene embrace straight and branched chain alkyl and alkylene radicals, respectively, containing 1 to 6 carbon atoms and the term amidoximo denotes the monovalent C(:NOH)NH group.

The tangible embodiments of this invention possess the inherent general physical characteristics of being, in the form of their acid addition salts, white crystalline solids. Spectral data reveal no unsaturation except as present in the :NOH portion of the amidoximo radical. These aforementioned physical characteristics, taken together with the nature of the starting materials and the mode of synthesis, positively confirm the structure of the compounds sought to be patented.

The tangible embodiments of this invention possess the inherent applied use characteristics of having pharmacological activity as anti-hypertensive agents and as agents for prolonging the effects of pharmacologically active barbituric acid derivatives as determined by recognized and accepted pharmacological test procedures.

The manner and process of making and using the invention will now be generally described so as to enable a person skilled in the art of chemistry to make and use the same as follows:

The starting materials for the compounds of this invention, N-(cyanoalkyl) endo-perhyclro-4,7-methanoisoindoles, are prepared according to the method described in my application entitled "N-Cyano-Alkyl-Endo-Perhydro-4,7-Methanoisoindoles, filed concurrently herewith.

The preparation of the tangible embodiments of this invention is illustrated as follows:

where A is lower alkylene.

The reaction depicted hereinabove is carried out by treating the starting material with hydroxylamine in the presence of an inert solvent, such as methylene chloride, benzene and the like, according to the method described by Mull et al. (I. Am. Chem. Soc. 80:3769 (1958)).

The tangible embodiments of this invention can, if desired, be converted into their non-toxic pharmaceutically acceptable acid addition or quaternary ammonium salts by conventional procedures. Typical acid addition salts include the hydrochloride, hydrobromide, citrate, maleate, sulfate, nitrate and the like. Typical quaternary ammonium salts are those formed with such alkyl halides as methyl iodide, n-hexyl bromide and the like. Such salts are the full equivalents of the free bases and are included within the scope of this invention.

The tangible embodiments of this invention, either as the free base or in the form of a non-toxic pharmaceutically acceptable acid addition or quaternary ammonium salt, may be combined with conventional pharmaceutical diluents and carriers, to form such dosage forms as tablets, capsules, solutions, suspensions, suppositories and the like.

The best mode contemplated by the inventor for carrying out this invention will now be set forth as follows:

EXAMPLE N (2 -Amid0xim0-Ethyl -End0-Perhydr04,7- M ethanoisoindole Dihydrochloride N-(2-cyanoethyl)-endo-perhydro-4,7-methanoisoindole (10 g., 0.0526 mole) is added to a solution of hydroxylamine hydrochloride (3.66 g., 0.053 mole) in ml. of anhydrous ethanol. A solution of sodium methoxide (2.04 g., 0.053 mole) in 30 ml. of anhydrous ethanol is added and the resulting mixture is refluxed for 2.5 hours. The reaction mixture is allowed to stand at room temperature for several hours and is then filtered. The filtrate is treated with hydrogen chloride and anhydrous ether is added to crystallize the product which is then recrystallized from ethanol/ether (anhydrous). Yield: 4.8 g. (31%) of white crystals, M.P. 208-2l0 C.

Analysis.-Calculated for C H N OCl C, 48.65%; H, 7.82%; Cl, 23.94%. Found: C, 48.53%; H, 8.04%; CI, 24.29%.

The subject matter which the applicant regards as his invention is particularly pointed out and distinctly claimed as follows.

I claim:

1. A compound of the formula NOH where A is lower alkylene.

2. N-(2' amidoximo-ethyl) endo perhydro 4,7 methanoisoindole.

References Cited in the file of this patent UNITED STATES PATENTS 2,897,195 Mull July 28, 1959 

1. A COMPOUND OF THE FORMULA 